G. Boehm

Oligosaccharides from Milk

Feeding infants breast milk of healthy mothers is associated with a lower incidence of infectious and allergic diseases. Although this effect is of multifactorial origin, it is widely accepted that the entire intestinal flora of breast-fed infants provides antiinfective properties and is an important stimulating factor for the postnatal development of the immune system. The effect of human milk on the postnatal development of the intestinal flora cannot be attributed to a single ingredient. It is generally accepted, however, that human milk oligosaccharides play a key role in this matter. Apart from their prebiotic effects, there is also evidence that human milk oligosaccharides act as receptor analogs to inhibit the adhesion of pathogens on the epithelial surface and interact directly with immune cells. Because of their complexity, oligosaccharides with structures identical to human milk oligosaccharides are not yet available as dietary ingredients. In the current search for alternatives, non-milk-derived oligosaccharides have gained much attention. As 1 example, a mixture of neutral galacto-oligosaccharides and long chain fructo-oligosaccharides have been identified as effective prebiotic ingredients during infancy. Furthermore, another class of oligosaccharides with a potential physiological benefit could be those found in animal milks. Most of the oligosaccharides detected in domestic animal milks have some structural features in common with human milk oligosaccharides. One important fact is the occurrence of sialic acids such as N-acetylneuraminic acids. However, total amounts and individual structures are still different from those in human milk oligosaccharides. Although these structural similarities between animal milk and human milk oligosaccharides are promising, further studies are needed to prove the equivalence of their function.

A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergy

Background:u2002 It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short‐chain galacto‐oligosaccharides and long‐chain fructo‐oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6u2003months of age in infants at risk for allergy.

Short term effects of dietary medium-chain fatty acids and n-3 long-chain polyunsaturated fatty acids on the fat metabolism of healthy volunteers

BackgroundThe amount and quality of dietary fatty acids can modulate the fat metabolism.ObjectiveThis dietary intervention is based on the different metabolic pathways of long-chain saturated fatty acids (LCFA), which are mostly stored in adipocytic triacylglycerols, medium-chain fatty acids (MCFA) which are preferentially available for hepatic mitochondrial β-oxidation and n-3 long-chain polyunsaturated fatty acids (n-3 LCPUFA) suggested to modulate fat oxidation and storage by stimulating the peroxisomal β-oxidation. Combined dietary MCFA and n-3 LCPUFA without LCFA may synergistically stimulate fatty acid oxidation resulting in blood lipid clearance and LCFA release from adipocytes.DesignIn a short term, parallel, randomized, double-blind trial effects on the fatty acid metabolism of 10 healthy volunteers (Body Mass Index 25–30) of a formula containing 72% MCFA and 22% n-3 LCPUFA without LCFA (intake: 1.500 kcal/day; fat: 55.5% of energy) were measured in comparison to an isoenergetic formula with equal fat amount and LCFA dominated lipid profile.ResultsThe plasma triacylglycerol (p < 0.1) and cholesterol (p < 0.05) content decreased in the test group. The n-3/n-6 LCPUFA (≥ C 20) ratio increased (p < 0.0001) after 4 days treatment. The LCFA content was similar in both groups despite missing LCFA in the test formula indicating LCFA release from adipocytes into the plasma. Both groups significantly reduced body weight considerably 4 kg (p < 0.01) and fat mass up to 50% of weight loss (p < 0.05).ConclusionCombined dietary 72% MCFA and 22% n-3 LCPUFA without LCFA stimulate the fatty acid oxidation and release from adipocytes without affecting any safety parameters measured.

Prebiotics and immune responses.

Feeding breast milk of healthy mothers is associated with a lower incidence of infectious and allergic diseases. Although this effect is of multifactorial origin, it is widely accepted that the entire intestinal flora of breastfed infants provides anti-infective properties and is an important stimulating factor for the postnatal development of the immune system. Clearly, the effect of human milk on the postnatal development of the intestinal flora cannot be attributed to a single ingredient. It is generally accepted, however, that human milk oligosaccharides play a key role in this matter (1). The composition of human milk oligosaccharides is very complex. As they are resistant against digestion, they can be detected in the faeces as well as in the urine of breast-fed infants (2). This low or absent digestibility is a prerequisite for prebiotic activities of dietary compounds (3). Apart from their prebiotic effects, there is also evidence that human milk oligosaccharides act as receptor analogues to inhibit the adhesion of pathogens on the epithelial surface (1) and interact directly with immune cells (Eiwegger Th, et al., unpublished data). Due to their complexity, oligosaccharides with structures indentical with human milk oligosaccharides are not available as dietary ingredients. Searching for alternatives, a mixture of neutral galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) have been identified as effective prebiotic ingredients during infancy (5). More recently, also acidic oligosaccharides such as pectin hydrolysate are under investigation (6). In several clinical trials it could be demonstrated that feeding a formula supplemented with a mixture of GOS and long-chain FOS results in an entire intestinal flora similar to that found in breast fed infants (7). Comparable to human milk oligosaccharides, GOS and FOS stay present during the whole gastrointestinal passage and are therefore detectable in the faeces of infants fed a GOS/FOS supplemented formula. With regard to stool characteristics, there was a significant influence of GOS/FOS in preterm as well as term infants: feeding the oligosaccharides-supplemented formula increased the stool frequency and softened the stool consistency in comparison to a standard formula so that stool characteristics could be achieved which were very similar to those of human milk fed infants (5). In a study in term infants the effect of different concentrations of the GOS/FOS mixture was tested in parallel by a traditional plating technique and a modern molecular biologic technique (7). Whereas with the plating technique, only living bacteria can be detected, all bacteria are counted with the molecular biologic technique. The results obtained by the two methods are shown in Figure 1. They clearly indicate that with the use of the GOS/FOS mixture, the number of bifidobacteria increases and the effect is much more pronounced for the living bacteria than for the total number of bacteria. Short-chain fatty acids (SCFA) are an important marker of the bacterial metabolism in the intestine. Invitro experiments focusing on the short SCFA synthesis by the faecal flora could demonstrate that the SCFA synthesis from GOS/FOS mixture was comparable to the synthesis from a quantitatively equivalent neutral human milk oligosaccharides fraction (7). Similar results were obtained in-vivo by measuring the fatty acid pattern in faeces from infants fed a formula supplemented with GOS/FOS: The faecal SCFA pattern was similar to that observed in breast fed infants (8). The results are in line with the observation that during a 28-day feeding period the faecal pH decreased in a group of term infants fed a GOS/FOS supplemented formula similar to breast fed infants, whereas the faecal pH in infants fed a nonsupplemented standard formula increased (5). Increased numbers of bifidobacteria and a decreased faecal pH are contributing to a reduction of clinically relevant pathogens, either expressed in absolute numbers or as percentage of total bacteria. In an animal study using the mouse vaccination model as recommended by international governmental guidelines (6), feeding GOS/FOS significantly stimulated the cellular (i.e., Th1/Th2) immune balance. In an animal model for allergic hypersensitivity using ovalbumin as allergen, dietary GOS/FOS inhibited the allergic inflammation (7). In summary, the data demonstrate that an infant formula supplemented with a mixture of GOS/FOS stimulates the entire intestinal flora and results in the production of physiologically important bacterial metabolites as well as a faecal pH similar to influences of human milk feeding. These effects are accompanied by stool characteristics close to those of breast-fed infants and by a Address correspondence and reprint requests to Prof. Gunther Boehm, Director Infant Nutrition Research Germany, Milupa GmbH & Co, KG Bahnstrasse 14-30, D-61381 Friedrichsdorf; Fax: 0049-6172991862 (e-mail: guenther.bohem@milupa.de). Journal of Pediatric Gastroenterology and Nutrition 39:S772–S773